Noise shielding techniques for ultra low current measurements in biochemical applications

ABSTRACT

A device having an integrated noise shield is disclosed. The device includes a plurality of vertical shielding structures substantially surrounding a semiconductor device. The device further includes an opening above the semiconductor device substantially filled with a conductive fluid, wherein the plurality of vertical shielding structures and the conductive fluid shield the semiconductor device from ambient radiation. In some embodiments, the device further includes a conductive bottom shield below the semiconductor device shielding the semiconductor device from ambient radiation. In some embodiments, the opening is configured to allow a biological sample to be introduced into the semiconductor device. In some embodiments, the vertical shielding structures comprise a plurality of vias, wherein each of the plurality of vias connects more than one conductive layers together. In some embodiments, the device comprises a nanopore device, and wherein the nanopore device comprises a single cell of a nanopore array.

CROSS REFERENCE TO OTHER APPLICATIONS

This application is a continuation of co-pending U.S. patent applicationSer. No. 14/558,222, entitled NOISE SHIELDING TECHNIQUES FOR ULTRA LOWCURRENT MEASUREMENTS IN BIOCHEMICAL APPLICATIONS , filed Dec. 2, 2014,which is a continuation of U.S. patent application Ser. No. 13/972,616,now U.S. Pat. No. 8,928,097, entitled NOISE SHIELDING TECHNIQUES FORULTRA LOW CURRENT MEASUREMENTS IN BIOCHEMICAL APPLICATIONS, filed Aug.21, 2013, which is a continuation of U.S. patent application Ser. No.13/396,522, now U.S. Pat. No. 8,541,849, entitled NOISE SHIELDINGTECHNIQUES FOR ULTRA LOW CURRENT MEASUREMENTS IN BIOCHEMICALAPPLICATIONS, filed Feb. 14, 2012, all of which are incorporated hereinby reference for all purposes.

BACKGROUND OF THE INVENTION

Advances in micro-miniaturization within the semiconductor industry inrecent years have enabled biotechnologists to pack traditionally bulkysensing tools into smaller and smaller form factors, onto so-calledbiochips. As device dimensions shrink, it would be desirable to develophigh sensitivity measurement techniques for biochips.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the invention are disclosed in the followingdetailed description and the accompanying drawings.

FIG. 1 is a block diagram illustrating an embodiment of a sensor circuit100 for measuring a physical property, such as a current, voltage, orcharge, within a single cell of a bio-sensor array using an integratingamplifier.

FIG. 2 is a diagram illustrating a cross-sectional view of an embodimentof a semiconductor device 200 with an integrated noise shield.

FIG. 3A is a diagram illustrating a top-view of an exemplaryconfiguration of vertical shielding structures 218.

FIG. 3B is a second diagram illustrating a top-view of another exemplaryconfiguration of vertical shielding structures 218.

FIG. 4 is a diagram illustrating a cross-sectional view of an embodimentof a semiconductor device 400 with an integrated noise shield.

DETAILED DESCRIPTION

The invention can be implemented in numerous ways, including as aprocess; an apparatus; a system; a composition of matter; a computerprogram product embodied on a computer readable storage medium; and/or aprocessor, such as a processor configured to execute instructions storedon and/or provided by a memory coupled to the processor. In thisspecification, these implementations, or any other form that theinvention may take, may be referred to as techniques. In general, theorder of the steps of disclosed processes may be altered within thescope of the invention. Unless stated otherwise, a component such as aprocessor or a memory described as being configured to perform a taskmay be implemented as a general component that is temporarily configuredto perform the task at a given time or a specific component that ismanufactured to perform the task. As used herein, the term ‘processor’refers to one or more devices, circuits, and/or processing coresconfigured to process data, such as computer program instructions.

A detailed description of one or more embodiments of the invention isprovided below along with accompanying figures that illustrate theprinciples of the invention. The invention is described in connectionwith such embodiments, but the invention is not limited to anyembodiment. The scope of the invention is limited only by the claims andthe invention encompasses numerous alternatives, modifications andequivalents. Numerous specific details are set forth in the followingdescription in order to provide a thorough understanding of theinvention. These details are provided for the purpose of example and theinvention may be practiced according to the claims without some or allof these specific details. For the purpose of clarity, technicalmaterial that is known in the technical fields related to the inventionhas not been described in detail so that the invention is notunnecessarily obscured.

Nanopore membrane devices having pore sizes on the order of 1 nanometerin internal diameter have shown promise in rapid nucleotide sequencing.A nanopore is a very small hole, and the nanopore can be created by apore-forming protein or as a hole in synthetic materials, such assilicon or graphene. When a voltage potential is applied across thenanopore immersed in a conducting fluid, a small ionic current arisingfrom the conduction of ions across the nanopore can be observed. When amolecule, such as a DNA or RNA molecule, passes through the nanopore,the molecule can partially or completely block the nanopore. Since thesize of the ionic current is sensitive to the pore size, the blockage ofthe nanopore by the DNA or RNA molecule causes a change in the magnitudeof the current through the nanopore. It has been shown that the ioniccurrent blockage can be correlated with the base pair sequence of theDNA molecule.

However, molecule characterization using nanopore membrane devices facevarious challenges. One of the challenges is measuring very low-levelsignals: the magnitude of the ionic current through the nanopore is verylow, typically on the order of a few tens or hundreds of picoamps (pA).Therefore, detecting any changes in such a low-level current through thenanopore becomes very challenging.

One effective circuit technique for measuring low-level current is usingan integrating amplifier. Using an integrating amplifier to measurelow-level current has several advantages. The integrating amplifieraverages the current over many measurement periods, which helps mitigatethe effects of noise to some degree. The integrating amplifier alsolimits the bandwidth to the bandwidth of interest without the need foradditional filtering. The circuitry for the integrating amplifier at themeasurement site is also small as compared to those corresponding toother measurement techniques, thus making it feasible to fabricate abio-sensor array with a large array of measurement cells, which ishighly desirable for identifying molecules in applications such assingle strand DNA characterization.

FIG. 1 is a block diagram illustrating an embodiment of a sensor circuit100 for measuring a physical property, such as a current, voltage, orcharge, within a single cell of a bio-sensor array using an integratingamplifier. As shown in FIG. 1, a physical property is detected bydetector 102 as detected signal 104. Sensor circuit 100 may be used tomeasure the mean value of detected signal 104 without sampling, asdescribed further below.

In some embodiments, an initiation flag 106 resets an integratingamplifier 108 and starts a continuous integration of detected signal 104over time. Integrated output 110 is compared with a trip threshold 114using a comparator 112. When integrated output 110 reaches tripthreshold 114, a trip flag 116 may be used as a feedback signal tointegrating amplifier 108 for terminating the integration of detectedsignal 104. For example, when trip flag 116 is “on” or asserted, theintegration is terminated. The duration of time between the assertion ofinitiation flag 106 and the assertion of trip flag 116 is proportionalto the mean value of detected signal 104, e.g., the mean value of acurrent. Accordingly, the “on” and “off” of trip flag 116 (only 1 bit ofinformation) may be sent from the cell to an external processor forcalculating the mean value of detected signal 104. Alternatively, the“on/off” information may be sent from the cell to an external storagefor delayed processing. For example, the clock cycles at whichinitiation flag 106 and trip flag 116 are respectively asserted may berecorded in an external storage. The number of clock cycles between thetwo asserted flags may then be used to determine the mean value ofdetected signal 104 at a later time.

In some embodiments, more accurate results may be obtained byintegrating detected signal 104 over multiple integrating cycles. Forexample, the determined mean value of detected signal 104 may be furtheraveraged over multiple integrating cycles. In some embodiments,initiation flag 106 is based at least in part on trip flag 116. Forexample, initiation flag 106 may be re-asserted in response to trip flag116 being asserted. In this example, trip flag 116 is used as a feedbacksignal for reinitializing integrating amplifier 108, such that anothercycle of integration of detected signal 104 may begin as soon as theprevious cycle of integration is terminated. Re-asserting initiationflag 106 immediately after trip flag 116 is asserted reduces the portionof time when detector 102 generates a signal that is not integrated andthus not measured. The integration occurs over approximately the entiretime that the signal is available. As a result, most of the informationof the signal is captured, thereby minimizing the time to obtain anaverage value for the measured signal.

The sensitivity of sensor circuit 100 is maximized by continuouslyintegrating detected signal 102 without sampling. This serves to limitthe bandwidth of the measured signal. With continuous reference to FIG.1, trip threshold 114 and an integration coefficient A set the bandwidthof the measured signal. As integration coefficient A decreases or astrip threshold 114 increases, the measured signal bandwidth decreases.

However, the low-current measuring circuit is susceptible to differentnoise sources, including external noise sources and noise sources withinthe measuring circuit itself External noise sources affecting theperformance of the low-current measuring circuit are numerous, includingalternating current (AC) line noise, ballast noise from florescent lightfixtures, electromagnetic interference (EMI), and the like.

Internal noise sources affecting the performance of the low-currentmeasuring circuit include voltage and noise components from theintegrating amplifier, as well as resistive noise from the measurementsource. These components are amplified by the noise gain of theintegrator, which is equal to (1+C_(in)/C_(fb)), where C_(in) is thetotal input capacitance, and C_(fb) is the integration capacitor (i.e.,the feedback capacitor (C_(fb)) for the integrating amplifier).

FIG. 2 is a diagram illustrating a cross-sectional view of an embodimentof a semiconductor device 200 with an integrated noise shield. In someembodiments, semiconductor device 200 is a nanopore device in a singlecell of a nanopore array, and the integrated noise shield shields thenanopore device from both external noise sources and internal noisesources. In some embodiments, the integrated noise shield disclosedherein can also be integrated into other types of bio-sensorsemiconductor arrays, such as bio-sensor semiconductor arrays in whichlow-level signal measurements susceptible to different noise sources aremade. A nanopore device is used hereinafter as an example forsemiconductor device 200. However, a nanopore device is selected forillustration purposes only; accordingly, the present application is notlimited to this specific example only.

The integrated noise shield surrounds and shields the portions ofsemiconductor device 200 that are susceptible to different noisesources. For example, with continued reference to FIG. 2, the portionsof semiconductor device 200 that are susceptible to noise include abiological sample 202, a measurement electrode 204, other measurementintegrated circuitries (not shown in the figure), and the like, andthese portions of semiconductor device 200 are surrounded and shieldedby the integrated noise shield. The integrated noise shield can beformed using any conductive material.

The integrated noise shield includes a bottom shield. With continuedreference to FIG. 2, the bottom shield includes one or more conductivelayers (206A and 206B) that are placed below the portions ofsemiconductor device 200 that are susceptible to noise. In someembodiments, conductive layer 206A is metal layer 5 (M5), which is themetal layer below the top metal layer 208 (M6) of semiconductor device200. Conductive layer 206B is metal layer 5′ (M5′ or MIM Cap layer),which is a metal layer sitting on top of M5 with a thin layer of oxide210 in between. In some embodiments, the bottom shield is formed usingconductive materials other than metal, including polycrystallinesilicon, and the like. In some embodiments, semiconductor device 200includes other conductive layers, such as a layer of substrate. Sincethe layer of substrate is typically thick and conductive, it acts as abottom shield layer for semiconductor device 200.

The integrated noise shield includes a top shield. The top shieldincludes a conductive layer 208 with an opening 212. With continuedreference to FIG. 2, the conductive layer 208 of the top shield is ametal layer placed above the portions of semiconductor device 200 thatare susceptible to noise. In some embodiments, conductive layer 208 ismetal layer 6 (M6), which is the top metal layer of semiconductor device200. In some embodiments, opening 212 allows biological sample 202 to beintroduced into semiconductor device 200 such that biological sample 202can be tested or analyzed by semiconductor device 200.

The top shield further includes a conductive liquid shield 214 depositedover and covering the portions of semiconductor device 200 that aresusceptible to noise, including biological sample 202. Withoutconductive liquid shield 214, opening 212 would expose semiconductordevice 200 to different noise sources. In addition, conductive layer 208(e.g., M6) cannot come into contact with the conductive liquid shield214. Therefore, conductive layer 208 is covered with a layer of oxide216 to insulate it from conductive liquid shield 214. In someembodiments, conductive liquid shield 214 is an electrolyte containingfree ions that make the electrolyte electrically conductive.

The integrated noise shield further includes a side shield. The sideshield includes a plurality of vertical shielding structures 218 forminga sidewall substantially surrounding the noise sensitive portions ofsemiconductor device 200. Note that in FIG. 2, only two verticalshielding structures 218 are illustrated. However, the number ofvertical shielding structures 218 can be more than two as well. In someembodiments, vertical shielding structures 218 include vias. Vias areformed by etching holes in insulating materials and depositing tungstenor other conductive material in the etched holes. The vias are used tomake vertical conductive connections between the various metal or otherconductive layers of semiconductor device 200. For example, withreference to FIG. 2, vias 218 interconnect conductive layer 208 andconductive layer 206A.

The plurality of vertical shielding structures 218 can be arranged indifferent configurations to achieve maximum shielding. FIG. 3A is adiagram illustrating a top-view of an exemplary configuration ofvertical shielding structures 218. As shown in FIG. 3A, the plurality ofvertical shielding structures 218 (e.g., vias) can be arranged in arectangular layout surrounding measurement electrode 204 and other noisesensitive portions of semiconductor device 200. However, otherconfiguration shapes can be used as well. For example, the plurality ofvertical shielding structures 218 can be arranged in a concentric ringsurrounding measurement electrode 204 and other noise sensitive portionsof semiconductor device 200.

FIG. 3B is a second diagram illustrating a top-view of another exemplaryconfiguration of vertical shielding structures 218. In thisconfiguration, the plurality of vertical shielding structures 218 arearranged in a plurality of concentric squares or rings, e.g., twoconcentric squares. In some embodiments, the vertical shieldingstructures 218 in one ring are offset from the vertical shieldingstructures 218 in a different ring, i.e., the rings of verticalshielding structures 218 are not aligned together. While a singlecontinuous shielding wall surrounding the noise sensitive portions ofsemiconductor device 200 may provide good shielding, the implementationof such a shielding wall may not be feasible due to various design ortechnical constraints. By offsetting one ring of vertical shieldingstructures 218 from another as shown in FIG. 3B, the shielding effect isclose to that achieved by forming a single continuous shielding wallsurrounding the noise sensitive portions of semiconductor device 200.

With continued reference to FIG. 2, conductive layer 208, which is aportion of the top shield, can be extended horizontally and radiallyoutwards in the directions indicated by arrows 218 and 220,respectively. Extending conductive layer 208 outwardly in this mannercreates a roof edge or awning shielding, which can further prevent someof the interference from passing through a plurality of gaps between theplurality of vertical shielding structures 218.

In some embodiments, the amount of extension of conductive layer 208described above can be traded off against the density of the pluralityof vertical shielding structures 218. Vias are typically made oftungsten, and polishing tungsten becomes more challenging when the viasare more densely populated. Therefore, in some embodiments, theplurality of vertical shielding structures 218 can be spaced furtherapart when conductive layer 208 is extended further outward to form anexpanded roof edge or awning to prevent some of the interference frominfiltrating in between the plurality of vertical shielding structures218.

In some embodiments, some of the conductive layers or oxide layersforming the integrated shield of semiconductor device 200 are exploitedto form a capacitor. For example, as shown in FIG. 2, the oxide layer210 between M5′ and M5 forms a capacitor 222. In some embodiments,semiconductor device 200 requires capacitors for various purposes. Forexample, the integrating amplifier in semiconductor device 200 mayrequire a capacitance, which can be provided by capacitor 222.

FIG. 4 is a diagram illustrating a cross-sectional view of an embodimentof a semiconductor device 400 with an integrated noise shield. Theintegrated noise shield surrounds and shields the portions ofsemiconductor device 400 that are susceptible to different noisesources.

The integrated noise shield includes a bottom shield. With continuedreference to FIG. 4, the bottom shield includes a substrate layer 402that is placed below the portions of semiconductor device 400 that aresusceptible to noise, including a layer 404 containing activesemiconductor circuits.

The integrated noise shield includes a top shield. In this embodiment,the top shield includes a conductive liquid shield 214 deposited overand covering the portions of semiconductor device 400 that aresusceptible to noise, including biological sample 202. Conductive layer406 (e.g., M6) cannot come into contact with conductive liquid shield214. Therefore, conductive layer 406 is covered with a layer of oxide216 to insulate it from conductive liquid shield 214, which may be anaqueous electrolyte solution as described earlier.

The integrated noise shield further includes a side shield. The sideshield includes a plurality of vertical shielding structures 218 (e.g.,vias) forming a sidewall substantially surrounding the noise sensitiveportions of semiconductor device 400.

The plurality of vertical shielding structures 218 can be arranged indifferent configurations to achieve maximum shielding. For example,configurations similar to those in FIG. 3A and FIG. 3B may be used.

With continued reference to FIG. 4, conductive layer 406 can be extendedradially outwards in the directions indicated by arrows 408 and 410,respectively. Extending conductive layer 406 outwards in this mannercreates a roof edge or awning, which can prevent some of theinterference from infiltrating in between the plurality of verticalshielding structures 218. In some embodiments, the amount of extensionof conductive layer 406 described above can be traded off against thedensity of the plurality of vertical shielding structures 218.

Although the foregoing embodiments have been described in some detailfor purposes of clarity of understanding, the invention is not limitedto the details provided. There are many alternative ways of implementingthe invention. The disclosed embodiments are illustrative and notrestrictive.

What is claimed is:
 1. (canceled)
 2. A nanopore device having anintegrated well, comprising: a plurality of vertical structuressubstantially surrounding the nanopore device, wherein the plurality ofvertical structures comprises a plurality of vertical vias arranged inone or more concentric rings surrounding the nanopore device, with thenanopore device substantially at the center; and an opening above thenanopore device substantially filled with a conductive fluid.
 3. Thenanopore device of claim 2, further comprising more than one conductivelayers, and wherein each of the plurality of vertical vias connects morethan one of the more than one conductive layers together.
 4. Thenanopore device of claim 3, further comprising an oxide layer between atleast some of the more than one conductive layers, and wherein the oxidelayer is configured to form a capacitor.
 5. The nanopore device of claim2, further comprising an oxide layer insulating a conductive layer fromthe conductive fluid.
 6. The nanopore device of claim 5, wherein theoxide layer is configured to form a capacitor.
 7. The nanopore device ofclaim 2, wherein the plurality of vertical vias are arranged in a singlering surrounding the nanopore device, with the nanopore devicesubstantially at the center of the single ring.
 8. The nanopore deviceof claim 2, wherein the vertical vias in a first ring of vias are offsetfrom the vertical vias in a second ring of vias.
 9. The nanopore deviceof claim 2, further comprising a conductive layer above the plurality ofvertical structures, and wherein the conductive layer is extendedhorizontally as an overhang above the plurality of vertical structures.10. A method for forming an integrated well for a nanopore device,comprising: providing a plurality of vertical structures substantiallysurrounding the nanopore device, wherein the plurality of verticalstructures comprises a plurality of vertical vias arranged in one ormore concentric rings surrounding the nanopore device, with the nanoporedevice substantially at the center; and providing an opening above thenanopore device substantially filled with a conductive fluid.
 11. Themethod of claim 10, further comprising: providing more than oneconductive layers, and wherein each of the plurality of vertical viasconnects more than one of the more than one conductive layers together.12. The method of claim 11, further comprising: providing an oxide layerbetween at least some of the more than one conductive layers, andwherein the oxide layer is configured to form a capacitor.
 13. Themethod of claim 10, further comprising: providing an oxide layerinsulating a conductive layer from the conductive fluid.
 14. The methodof claim 13, wherein the oxide layer is configured to form a capacitor.15. The method of claim 10, wherein the plurality of vertical vias arearranged in a single ring surrounding the nanopore device, with thenanopore device substantially at the center of the single ring.
 16. Themethod of claim 10, wherein the vertical vias in a first ring of viasare offset from the vertical vias in a second ring of vias.
 17. Themethod of claim 10, further comprising: providing a conductive layerabove the plurality of vertical structures, and wherein the conductivelayer is extended horizontally as an overhang above the plurality ofvertical structures.